Renovascular disease (RVD) is the most common potentially reversible cause of hypertension and renal failure in the US. Its diagnosis is problematic because renal artery stenosis (RAS) alone is insufficient for diagnosis. Essential hypertension and RAS often coexist, hence anatomic studies such as x-ray angiography do not accurately predict response to revascularization. To date, no test provides both accurate anatomic and functional assessment to diagnose RVD. Management of RAS patients is also a dilemma. The inability to differentiate RVD from incidental RAS has also contributed to the widespread uncertainty treatment, and lack of a sensitive test for detecting individual kidney response has further limited clinical trials. In the first funding period we developed a robust and quantitative low dose Gd-enhanced MR renography method for measuring single kidney glomerular filtration rate (GFR) and implemented a dual-injection method for ACE-inhibitor- enhanced MR renography to diagnose RVD. Our functional study can be performed in conjunction with renal MRA for anatomic evaluation with promising early results. We have also shown the feasibility of combining furosemide-enhanced BOLD MR with ACE-I MR renography for measuring renal ischemia in patients with RAS and have also investigated new non-Gd-enhanced MRA methods. In the next funding period, we propose to test a comprehensive-anatomic and functional-MR protocol to diagnose RVD and also to use MR longitudinally to measure single kidney functional outcomes. Broad, long-term objectives: To reduce the morbidity and mortality associated with hypertension and renal failure due to RVD by correctly diagnosing the disease and by determining which patients are likely to benefit from revascularization therapy and which patients should be treated with medication alone. Specific Aims/Methods: (1) To determine the accuracy of a single comprehensive exam that combines MRA with ACE-inhibitor MR renography and furosemide-BOLD MRI for the diagnosis of RVD. We will perform a prospective study in 264 subjects over 3 years and compare our MR results with MRA and x-ray angiography, using response to revascularization measures of blood pressure and renal function as the reference standard. (2) To perform a longitudinal study using MR renography and furosemide-BOLD MRI to study ipsi- and contralateral single kidney GFR in RAS patients who undergo revascularization or who are medically managed. We will use measurements of single kidney GFR and oxygenation to assess responses to therapies with the hypothesis that our methods will detect otherwise subclinical improvements in renal function after revascularization and otherwise subclinical declines in patients with RVD managed medically. At its conclusion, our study highly likely to show that a comprehensive MR exam, by uniquely providing both anatomic and functional information in a single test, will accurately diagnose RVD and provide a valuable tool for measuring outcomes following therapy. PUBLIC HEALTH RELEVANCE: The proposed project will be important for helping to improve the accuracy of diagnosis of a common disease, renovascular disease, which causes hypertension and kidney failure. With novel MRI methods, we can detect narrowings of the renal arteries and assess their impact on the functioning of kidneys in order to predict who should undergo an interventional treatment to open the arteries and who should be treated with medications only. Our anatomic and functional MRI techniques also have the potential to offer new insights into the diagnosis and treatment of other kidney diseases such as diabetes and kidney transplant dysfunction.